2025-11-29
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This presentation summarizes:
Last Gift Cohort
Body Donation
Autopsy
Tissue Collection
HIV Sequencing
Phylogenetics and Modeling
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Note
Conceptual motivation
In a transition model, exposure represents the “opportunity” for observing a migration event between compartments. We considered the following definition:
\[ n_{\text{states}, i} : \text{number of Markov states in run } i \times \text{number of sequences from CNS} \times \text{number of sequences from Periphery} \]
data %>%
mutate(
pairs_cns = ntissues_cns * (ntissues_cns - 1) / 2,
pairs_periph = ntissues_periph * (ntissues_periph - 1) / 2,
exposure = case_when(
migration_type == "cross_BBB" & direction == "CNS to Periph" ~
n_states * nseq_cns * nseq_periph,
migration_type == "cross_BBB" & direction == "Periphery to CNS" ~
n_states * nseq_periph * nseq_cns,
migration_type == "within_CNS" ~
n_states * pairs_cns * (nseq_cns^2),
migration_type == "within_peripheral" ~
n_states * pairs_periph * (nseq_periph^2)
)
)
Notes
\[ \log(\mu_i) = \beta_0 + \beta_1 \cdot \text{Marker}_i + b_{\text{pid}(i)} + \log(\text{Exposure}_i) \]
fit_models <- function(marker, data_in) {
formula <- as.formula(
paste0(
"n_events ~ ", marker,
" + age + sex + last_cd4_t_cell_count + duration_infection_years +
(1 | pid) + offset(log_exposure)"
)
)
glmmTMB(
formula,
data = data_in,
family = nbinom2(),
control = glmmTMBControl(
optimizer = optim,
optArgs = list(method = "BFGS", maxit = 5000)
)
)
}
fit_models <- function(marker, data_in) {
formula <- as.formula(
paste0(
"n_events ~ ", marker,
" + age + sex + last_cd4_t_cell_count + duration_infection_years +
dna_level_from + dna_level_to +
(1 | pid) + offset(log_exposure)"
)
)
glmmTMB(
formula,
data = data_in,
family = nbinom2(),
control = glmmTMBControl(
optimizer = optim,
optArgs = list(method = "BFGS", maxit = 5000)
)
)
}
| Associations between CSF biomarkers and counts of migration events from the CNS to the periphery | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Negative Binomial Models | |||||||||
| Marker | Samples Detectable1 | Effect | Status | exp(Beta) | 95% CI | p-value | Significance | Direction | |
| Eotaxin (CCL11) | 13 | Ok | ✅ | 1.035 | 0.7967–1.35 | 0.795 | ⬆ | ||
| GM-CSF | 8 | Ok | ✅ | 0.884 | 0.7446–1.05 | 0.161 | ⬇ | ||
| GRO-alpha (CXCL1) | 13 | Ok | ✅ | 0.988 | 0.9808–1.00 | 0.001 | ** | ⬇ | |
| IL-1α | 1 | Sparse Data | ❌ | 0.160 | 0.0022–11.58 | 0.401 | ⬇ | ||
| IL-1β | 5 | Ok | ✅ | 0.806 | 0.6734–0.96 | 0.018 | * | ⬇ | |
| IL-1RA | 12 | Ok | ✅ | 1.000 | 0.9995–1.00 | 0.000 | *** | ⬇ | |
| IL-2 | 2 | Sparse Data | ❌ | 0.418 | 0.2951–0.59 | 0.000 | *** | ⬇ | |
| IL-5 | 5 | Ok | ✅ | 0.985 | 0.8082–1.20 | 0.885 | ⬇ | ||
| IL-6 | 12 | Ok | ✅ | 0.998 | 0.9971–1.00 | 0.000 | *** | ⬇ | |
| IL-7 | 13 | Ok | ✅ | 0.356 | 0.0618–2.05 | 0.248 | ⬇ | ||
| IL-8 (CXCL8) | 13 | Ok | ✅ | 0.998 | 0.9952–1.00 | 0.043 | * | ⬇ | |
| IL-9 | 1 | Sparse Data | ❌ | 1.104 | 0.5813–2.10 | 0.762 | ⬆ | ||
| IL-10 | 8 | Ok | ✅ | 0.481 | 0.2551–0.91 | 0.023 | * | ⬇ | |
| IL-15 | 5 | Ok | ✅ | 0.442 | 0.1617–1.21 | 0.112 | ⬇ | ||
| IL-17A/CTLA-8 | 1 | Sparse Data | ❌ | 0.409 | 0.0534–3.13 | 0.389 | ⬇ | ||
| IL-18 | 13 | Ok | ✅ | 1.009 | 0.9871–1.03 | 0.435 | ⬆ | ||
| IL-31 | 1 | Sparse Data | ❌ | 0.932 | 0.6748–1.29 | 0.668 | ⬇ | ||
| IP-10 (CXCL10) | 13 | Ok | ✅ | 1.000 | 0.9967–1.00 | 0.841 | ⬇ | ||
| MCP-1 (CCL2) | 13 | Ok | ✅ | 1.000 | 0.9985–1.00 | 0.908 | ⬇ | ||
| MIP-1α (CCL3) | 13 | Ok | ✅ | 0.868 | 0.7918–0.95 | 0.002 | ** | ⬇ | |
| MIP-1β (CCL4) | 13 | Ok | ✅ | 0.964 | 0.9420–0.99 | 0.002 | ** | ⬇ | |
| RANTES (CCL5) | 13 | Ok | ✅ | 1.007 | 0.9176–1.11 | 0.881 | ⬆ | ||
| SDF-1α | 13 | Ok | ✅ | 1.000 | 0.9993–1.00 | 0.798 | ⬆ | ||
| TNF-α | 2 | Sparse Data | ❌ | 0.328 | 0.2148–0.50 | 0.000 | *** | ⬇ | |
| 1 Number of samples with ≥1 measure(s) above the LOD across the 3 replicates. | |||||||||
| Associations between CSF biomarkers and counts of migration events from the periphery to the CNS | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Negative Binomial Models | |||||||||
| Marker | Samples Detectable1 | Effect | Status | exp(Beta) | 95% CI | p-value | Significance | Direction | |
| Eotaxin (CCL11) | 16 | Ok | ✅ | 1.002 | 0.875–1.15 | 0.972 | ⬆ | ||
| GM-CSF | 11 | Ok | ✅ | 0.849 | 0.752–0.96 | 0.008 | ** | ⬇ | |
| GRO-alpha (CXCL1) | 16 | Ok | ✅ | 0.987 | 0.980–0.99 | 0.000 | *** | ⬇ | |
| IL-1α | 1 | Sparse Data | ❌ | 0.258 | 0.011–6.02 | 0.399 | ⬇ | ||
| IL-1β | 7 | Ok | ✅ | 0.843 | 0.721–0.99 | 0.034 | * | ⬇ | |
| IL-1RA | 15 | Ok | ✅ | 1.000 | 1.000–1.00 | 0.007 | ** | ⬇ | |
| IL-2 | 2 | Sparse Data | ❌ | 0.374 | 0.283–0.49 | 0.000 | *** | ⬇ | |
| IL-5 | 7 | Ok | ✅ | 0.893 | 0.678–1.18 | 0.420 | ⬇ | ||
| IL-6 | 15 | Ok | ✅ | 0.998 | 0.997–1.00 | 0.000 | *** | ⬇ | |
| IL-7 | 16 | Ok | ✅ | 1.460 | 0.378–5.64 | 0.583 | ⬆ | ||
| IL-8 (CXCL8) | 16 | Ok | ✅ | 0.999 | 0.998–1.00 | 0.140 | ⬇ | ||
| IL-9 | 1 | Sparse Data | ❌ | 1.331 | 0.731–2.42 | 0.349 | ⬆ | ||
| IL-10 | 10 | Ok | ✅ | 0.823 | 0.685–0.99 | 0.038 | * | ⬇ | |
| IL-15 | 7 | Ok | ✅ | 0.249 | 0.119–0.52 | 0.000 | *** | ⬇ | |
| IL-17A/CTLA-8 | 2 | Sparse Data | ❌ | 0.745 | 0.250–2.22 | 0.596 | ⬇ | ||
| IL-18 | 16 | Ok | ✅ | 1.008 | 0.991–1.03 | 0.359 | ⬆ | ||
| IL-31 | 1 | Sparse Data | ❌ | 0.911 | 0.689–1.20 | 0.509 | ⬇ | ||
| IP-10 (CXCL10) | 16 | Ok | ✅ | 1.000 | 0.999–1.00 | 0.746 | ⬇ | ||
| MCP-1 (CCL2) | 16 | Ok | ✅ | 1.000 | 0.999–1.00 | 0.987 | ⬇ | ||
| MIP-1α (CCL3) | 16 | Ok | ✅ | 0.903 | 0.827–0.99 | 0.024 | * | ⬇ | |
| MIP-1β (CCL4) | 16 | Ok | ✅ | 0.987 | 0.969–1.01 | 0.157 | ⬇ | ||
| RANTES (CCL5) | 16 | Ok | ✅ | 1.001 | 0.935–1.07 | 0.987 | ⬆ | ||
| SDF-1α | 16 | Ok | ✅ | 1.000 | 0.999–1.00 | 0.296 | ⬇ | ||
| TNF-α | 3 | Sparse Data | ❌ | 0.380 | 0.220–0.66 | 0.001 | *** | ⬇ | |
| 1 Number of samples with ≥1 measure(s) above the LOD across the 3 replicates. | |||||||||
| Associations between CSF biomarkers and counts of migration events across the BBB | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Negative Binomial Models | |||||||||
| Marker | Samples Detectable1 | Effect | Status | exp(Beta) | 95% CI | p-value | Significance | Direction | |
| Eotaxin (CCL11) | 16 | Ok | ✅ | 1.079 | 0.9085–1.28 | 0.387 | ⬆ | ||
| GM-CSF | 11 | Ok | ✅ | 0.853 | 0.7522–0.97 | 0.013 | * | ⬇ | |
| GRO-alpha (CXCL1) | 16 | Ok | ✅ | 0.989 | 0.9803–1.00 | 0.007 | ** | ⬇ | |
| IL-1α | 1 | Sparse Data | ❌ | 0.295 | 0.0061–14.32 | 0.538 | ⬇ | ||
| IL-1β | 7 | Ok | ✅ | 0.824 | 0.6595–1.03 | 0.089 | . | ⬇ | |
| IL-1RA | 15 | Ok | ✅ | 1.000 | 0.9995–1.00 | 0.000 | *** | ⬇ | |
| IL-2 | 2 | Sparse Data | ❌ | 0.385 | 0.3005–0.49 | 0.000 | *** | ⬇ | |
| IL-5 | 7 | Ok | ✅ | 0.913 | 0.7685–1.08 | 0.300 | ⬇ | ||
| IL-6 | 15 | Ok | ✅ | 0.998 | 0.9973–1.00 | 0.000 | *** | ⬇ | |
| IL-7 | 16 | Ok | ✅ | 1.273 | 0.2751–5.89 | 0.757 | ⬆ | ||
| IL-8 (CXCL8) | 16 | Ok | ✅ | 0.999 | 0.9970–1.00 | 0.241 | ⬇ | ||
| IL-9 | 1 | Sparse Data | ❌ | 1.235 | 0.7163–2.13 | 0.448 | ⬆ | ||
| IL-10 | 10 | Ok | ✅ | 0.794 | 0.6189–1.02 | 0.069 | . | ⬇ | |
| IL-15 | 7 | Ok | ✅ | 0.286 | 0.1314–0.62 | 0.002 | ** | ⬇ | |
| IL-17A/CTLA-8 | 2 | Sparse Data | ❌ | 1.011 | 0.2677–3.82 | 0.987 | ⬆ | ||
| IL-18 | 16 | Ok | ✅ | 1.010 | 0.9911–1.03 | 0.313 | ⬆ | ||
| IL-31 | 1 | Sparse Data | ❌ | 0.955 | 0.7104–1.28 | 0.762 | ⬇ | ||
| IP-10 (CXCL10) | 16 | Ok | ✅ | 1.000 | 0.9988–1.00 | 0.576 | ⬆ | ||
| MCP-1 (CCL2) | 16 | Ok | ✅ | 1.000 | 0.9987–1.00 | 0.763 | ⬇ | ||
| MIP-1α (CCL3) | 16 | Ok | ✅ | 0.883 | 0.7876–0.99 | 0.032 | * | ⬇ | |
| MIP-1β (CCL4) | 16 | Ok | ✅ | 0.988 | 0.9626–1.01 | 0.343 | ⬇ | ||
| RANTES (CCL5) | 16 | Ok | ✅ | 1.024 | 0.9410–1.11 | 0.581 | ⬆ | ||
| SDF-1α | 16 | Ok | ✅ | 1.000 | 0.9976–1.00 | 0.996 | ⬇ | ||
| TNF-α | 3 | Sparse Data | ❌ | 0.358 | 0.2383–0.54 | 0.000 | *** | ⬇ | |
| 1 Number of samples with ≥1 measure(s) above the LOD across the 3 replicates. | |||||||||
| Associations between CSF biomarkers and counts of migration events within CNS | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Negative Binomial Models | |||||||||
| Marker | Samples Detectable1 | Effect | Status | exp(Beta) | 95% CI | p-value | Significance | Direction | |
| Eotaxin (CCL11) | 16 | Ok | ✅ | 1.024 | 0.84274–1.25 | 0.809 | ⬆ | ||
| GM-CSF | 11 | Ok | ✅ | 0.912 | 0.74469–1.12 | 0.373 | ⬇ | ||
| GRO-alpha (CXCL1) | 16 | Ok | ✅ | 0.986 | 0.97556–1.00 | 0.008 | ** | ⬇ | |
| IL-1α | 1 | Sparse Data | ❌ | 0.001 | 0.00002–0.05 | 0.001 | *** | ⬇ | |
| IL-1β | 7 | Ok | ✅ | 0.881 | 0.69896–1.11 | 0.282 | ⬇ | ||
| IL-1RA | 15 | Ok | ✅ | 0.999 | 0.99921–1.00 | 0.000 | *** | ⬇ | |
| IL-2 | 2 | Sparse Data | ❌ | 0.411 | 0.24355–0.69 | 0.001 | *** | ⬇ | |
| IL-5 | 7 | Ok | ✅ | 1.205 | 0.82781–1.75 | 0.331 | ⬆ | ||
| IL-6 | 15 | Ok | ✅ | 0.998 | 0.99624–1.00 | 0.032 | * | ⬇ | |
| IL-7 | 16 | Ok | ✅ | 0.369 | 0.08496–1.61 | 0.184 | ⬇ | ||
| IL-8 (CXCL8) | 16 | Ok | ✅ | 0.999 | 0.99734–1.00 | 0.512 | ⬇ | ||
| IL-9 | 1 | Sparse Data | ❌ | 0.562 | 0.26925–1.17 | 0.125 | ⬇ | ||
| IL-10 | 10 | Ok | ✅ | 0.999 | 0.72760–1.37 | 0.996 | ⬇ | ||
| IL-15 | 7 | Ok | ✅ | 0.279 | 0.07528–1.03 | 0.056 | . | ⬇ | |
| IL-17A/CTLA-8 | 2 | Sparse Data | ❌ | 1.601 | 0.24895–10.29 | 0.620 | ⬆ | ||
| IL-18 | 16 | Ok | ✅ | 1.013 | 0.98636–1.04 | 0.334 | ⬆ | ||
| IL-31 | 1 | Sparse Data | ❌ | 0.882 | 0.64825–1.20 | 0.425 | ⬇ | ||
| IP-10 (CXCL10) | 16 | Ok | ✅ | 1 | 0.99786–1.00 | 0.840 | ⬆ | ||
| MCP-1 (CCL2) | 16 | NA Estimates | ❌ | 0.999 | NA–NA | NaN | ⬇ | ||
| MIP-1α (CCL3) | 16 | Wide CI | ❌ | >1e6 | <1e-6–+Inf | 0.963 | ⬆ | ||
| MIP-1β (CCL4) | 16 | Ok | ✅ | 0.971 | 0.93720–1.01 | 0.108 | ⬇ | ||
| RANTES (CCL5) | 16 | NA Estimates | ❌ | 0.933 | NA–NA | NaN | ⬇ | ||
| SDF-1α | 16 | Ok | ✅ | 1 | 0.99906–1.00 | 0.605 | ⬆ | ||
| TNF-α | 3 | Sparse Data | ❌ | 0.445 | 0.19842–1.00 | 0.049 | * | ⬇ | |
| 1 Number of samples with ≥1 measure(s) above the LOD across the 3 replicates. | |||||||||
| Associations between CSF biomarkers and counts of migration events from the CNS to the periphery | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Negative Binomial Models (per transition) | |||||||||
| Marker | Samples Detectable1 | Effect | Status | exp(Beta) | 95% CI | p-value | Significance | Direction | |
| Eotaxin (CCL11) | 13 | Ok | ✅ | 1.050 | 0.925–1.19 | 0.447 | ⬆ | ||
| GM-CSF | 8 | Ok | ✅ | 0.943 | 0.870–1.02 | 0.154 | ⬇ | ||
| GRO-alpha (CXCL1) | 13 | Ok | ✅ | 0.996 | 0.992–1.00 | 0.076 | . | ⬇ | |
| IL-1α | 1 | Sparse Data | ❌ | 0.074 | 0.013–0.41 | 0.003 | ** | ⬇ | |
| IL-1β | 5 | Ok | ✅ | 0.974 | 0.848–1.12 | 0.711 | ⬇ | ||
| IL-1RA | 12 | Ok | ✅ | 1.000 | 1.000–1.00 | 0.000 | *** | ⬇ | |
| IL-2 | 2 | Sparse Data | ❌ | 0.689 | 0.530–0.89 | 0.005 | ** | ⬇ | |
| IL-5 | 5 | Ok | ✅ | 0.990 | 0.899–1.09 | 0.831 | ⬇ | ||
| IL-6 | 12 | Ok | ✅ | 0.999 | 0.999–1.00 | 0.032 | * | ⬇ | |
| IL-7 | 13 | Ok | ✅ | 1.515 | 0.581–3.95 | 0.395 | ⬆ | ||
| IL-8 (CXCL8) | 13 | Ok | ✅ | 0.998 | 0.997–1.00 | 0.000 | *** | ⬇ | |
| IL-9 | 1 | Sparse Data | ❌ | 0.785 | 0.551–1.12 | 0.178 | ⬇ | ||
| IL-10 | 8 | Ok | ✅ | 0.657 | 0.489–0.88 | 0.005 | ** | ⬇ | |
| IL-15 | 5 | Ok | ✅ | 0.702 | 0.424–1.16 | 0.169 | ⬇ | ||
| IL-17A/CTLA-8 | 1 | Sparse Data | ❌ | 0.660 | 0.235–1.85 | 0.430 | ⬇ | ||
| IL-18 | 13 | Ok | ✅ | 1.011 | 1.001–1.02 | 0.034 | * | ⬆ | |
| IL-31 | 1 | Sparse Data | ❌ | 1.042 | 0.882–1.23 | 0.626 | ⬆ | ||
| IP-10 (CXCL10) | 13 | Ok | ✅ | 1.000 | 0.999–1.00 | 0.963 | ⬆ | ||
| MCP-1 (CCL2) | 13 | Ok | ✅ | 0.999 | 0.999–1.00 | 0.000 | *** | ⬇ | |
| MIP-1α (CCL3) | 13 | Ok | ✅ | 0.957 | 0.887–1.03 | 0.255 | ⬇ | ||
| MIP-1β (CCL4) | 13 | Ok | ✅ | 0.984 | 0.969–1.00 | 0.034 | * | ⬇ | |
| RANTES (CCL5) | 13 | Ok | ✅ | 1.006 | 0.962–1.05 | 0.794 | ⬆ | ||
| SDF-1α | 13 | Ok | ✅ | 1.000 | 0.999–1.00 | 0.930 | ⬆ | ||
| TNF-α | 2 | Sparse Data | ❌ | 0.610 | 0.457–0.81 | 0.001 | *** | ⬇ | |
| 1 Number of samples with ≥1 measure(s) above the LOD across the 3 replicates. | |||||||||
| Negative Binomial Models (per transition) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Associations between CSF biomarkers and counts of migration events from the periphery to the CNS | |||||||||
| Marker | Samples Detectable1 | Effect | Status | exp(Beta) | 95% CI | p-value | Significance | Direction | |
| Eotaxin (CCL11) | 15 | Ok | ✅ | 1.030 | 0.931–1.14 | 0.565 | ⬆ | ||
| GM-CSF | 10 | Ok | ✅ | 0.912 | 0.849–0.98 | 0.013 | * | ⬇ | |
| GRO-alpha (CXCL1) | 15 | Ok | ✅ | 0.995 | 0.991–1.00 | 0.020 | * | ⬇ | |
| IL-1α | 1 | Sparse Data | ❌ | 0.744 | 0.069–7.97 | 0.807 | ⬇ | ||
| IL-1β | 7 | Ok | ✅ | 0.890 | 0.776–1.02 | 0.095 | . | ⬇ | |
| IL-1RA | 14 | Ok | ✅ | 1.000 | 1.000–1.00 | 0.197 | ⬇ | ||
| IL-2 | 2 | Sparse Data | ❌ | 0.607 | 0.490–0.75 | 0.000 | *** | ⬇ | |
| IL-5 | 6 | Ok | ✅ | 0.953 | 0.864–1.05 | 0.342 | ⬇ | ||
| IL-6 | 14 | Ok | ✅ | 0.999 | 0.999–1.00 | 0.025 | * | ⬇ | |
| IL-7 | 15 | Ok | ✅ | 1.297 | 0.464–3.62 | 0.620 | ⬆ | ||
| IL-8 (CXCL8) | 15 | Ok | ✅ | 0.999 | 0.998–1.00 | 0.387 | ⬇ | ||
| IL-9 | 1 | Sparse Data | ❌ | 1.121 | 0.794–1.58 | 0.516 | ⬆ | ||
| IL-10 | 10 | Ok | ✅ | 0.880 | 0.738–1.05 | 0.159 | ⬇ | ||
| IL-15 | 6 | Ok | ✅ | 0.528 | 0.346–0.80 | 0.003 | ** | ⬇ | |
| IL-17A/CTLA-8 | 2 | Sparse Data | ❌ | 1.072 | 0.469–2.45 | 0.870 | ⬆ | ||
| IL-18 | 15 | Ok | ✅ | 1.007 | 0.996–1.02 | 0.223 | ⬆ | ||
| IL-31 | 1 | Sparse Data | ❌ | 0.945 | 0.794–1.13 | 0.527 | ⬇ | ||
| IP-10 (CXCL10) | 15 | Ok | ✅ | 1.000 | 0.999–1.00 | 0.862 | ⬆ | ||
| MCP-1 (CCL2) | 15 | Ok | ✅ | 1.000 | 0.999–1.00 | 0.958 | ⬇ | ||
| MIP-1α (CCL3) | 15 | Ok | ✅ | 0.917 | 0.854–0.99 | 0.018 | * | ⬇ | |
| MIP-1β (CCL4) | 15 | Ok | ✅ | 0.991 | 0.976–1.01 | 0.245 | ⬇ | ||
| RANTES (CCL5) | 15 | Ok | ✅ | 1.004 | 0.957–1.05 | 0.875 | ⬆ | ||
| SDF-1α | 15 | Ok | ✅ | 1.000 | 0.999–1.00 | 0.551 | ⬇ | ||
| TNF-α | 3 | Sparse Data | ❌ | 0.574 | 0.418–0.79 | 0.001 | *** | ⬇ | |
| 1 Number of samples with ≥1 measure(s) above the LOD across the 3 replicates. | |||||||||
| Associations between CSF biomarkers and counts of migration events across the BBB | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Negative Binomial Models (per transition) | |||||||||
| Marker | Samples Detectable1 | Effect | Status | exp(Beta) | 95% CI | p-value | Significance | Direction | |
| Eotaxin (CCL11) | 15 | Ok | ✅ | 1.030 | 0.936–1.13 | 0.542 | ⬆ | ||
| GM-CSF | 10 | Ok | ✅ | 0.925 | 0.863–0.99 | 0.029 | * | ⬇ | |
| GRO-alpha (CXCL1) | 15 | Ok | ✅ | 0.995 | 0.991–1.00 | 0.026 | * | ⬇ | |
| IL-1α | 1 | Sparse Data | ❌ | 0.465 | 0.054–3.98 | 0.485 | ⬇ | ||
| IL-1β | 7 | Ok | ✅ | 0.903 | 0.795–1.03 | 0.115 | ⬇ | ||
| IL-1RA | 14 | Ok | ✅ | 1.000 | 1.000–1.00 | 0.013 | * | ⬇ | |
| IL-2 | 2 | Sparse Data | ❌ | 0.624 | 0.510–0.76 | 0.000 | *** | ⬇ | |
| IL-5 | 6 | Ok | ✅ | 0.965 | 0.878–1.06 | 0.455 | ⬇ | ||
| IL-6 | 14 | Ok | ✅ | 0.999 | 0.999–1.00 | 0.023 | * | ⬇ | |
| IL-7 | 15 | Ok | ✅ | 1.306 | 0.503–3.39 | 0.584 | ⬆ | ||
| IL-8 (CXCL8) | 15 | Ok | ✅ | 0.999 | 0.998–1.00 | 0.206 | ⬇ | ||
| IL-9 | 1 | Sparse Data | ❌ | 1.061 | 0.773–1.46 | 0.712 | ⬆ | ||
| IL-10 | 10 | Ok | ✅ | 0.891 | 0.760–1.04 | 0.153 | ⬇ | ||
| IL-15 | 6 | Ok | ✅ | 0.570 | 0.374–0.87 | 0.009 | ** | ⬇ | |
| IL-17A/CTLA-8 | 2 | Sparse Data | ❌ | 0.967 | 0.450–2.08 | 0.932 | ⬇ | ||
| IL-18 | 15 | Ok | ✅ | 1.007 | 0.997–1.02 | 0.167 | ⬆ | ||
| IL-31 | 1 | Sparse Data | ❌ | 0.958 | 0.815–1.13 | 0.599 | ⬇ | ||
| IP-10 (CXCL10) | 15 | Ok | ✅ | 1.000 | 0.999–1.00 | 0.866 | ⬆ | ||
| MCP-1 (CCL2) | 15 | Ok | ✅ | 1.000 | 0.999–1.00 | 0.796 | ⬇ | ||
| MIP-1α (CCL3) | 15 | Ok | ✅ | 0.923 | 0.865–0.99 | 0.017 | * | ⬇ | |
| MIP-1β (CCL4) | 15 | Ok | ✅ | 0.990 | 0.976–1.00 | 0.149 | ⬇ | ||
| RANTES (CCL5) | 15 | Ok | ✅ | 1.006 | 0.962–1.05 | 0.779 | ⬆ | ||
| SDF-1α | 15 | Ok | ✅ | 1.000 | 1.000–1.00 | 0.671 | ⬇ | ||
| TNF-α | 3 | Sparse Data | ❌ | 0.590 | 0.446–0.78 | 0.000 | *** | ⬇ | |
| 1 Number of samples with ≥1 measure(s) above the LOD across the 3 replicates. | |||||||||
| Associations between CSF biomarkers and counts of migration events within CNS | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Negative Binomial Models (per transition) | |||||||||
| Marker | Samples Detectable1 | Effect | Status | exp(Beta) | 95% CI | p-value | Significance | Direction | |
| Eotaxin (CCL11) | 15 | Ok | ✅ | 1.291 | 0.88–1.88 | 0.185 | ⬆ | ||
| GM-CSF | 10 | Ok | ✅ | 0.702 | 0.35–1.42 | 0.325 | ⬇ | ||
| GRO-alpha (CXCL1) | 15 | Ok | ✅ | 0.538 | 0.28–1.03 | 0.060 | . | ⬇ | |
| IL-1α | 1 | Sparse Data | ❌ | 0.661 | 0.51–0.86 | 0.002 | ** | ⬇ | |
| IL-1β | 6 | Ok | ✅ | 0.950 | 0.51–1.77 | 0.871 | ⬇ | ||
| IL-1RA | 14 | Ok | ✅ | 0.469 | 0.33–0.67 | 0.000 | *** | ⬇ | |
| IL-2 | 2 | Sparse Data | ❌ | 0.583 | 0.36–0.93 | 0.025 | * | ⬇ | |
| IL-5 | 7 | Ok | ✅ | 0.837 | 0.40–1.77 | 0.641 | ⬇ | ||
| IL-6 | 14 | Ok | ✅ | 0.513 | 0.28–0.93 | 0.029 | * | ⬇ | |
| IL-7 | 15 | Ok | ✅ | 1.186 | 0.73–1.92 | 0.491 | ⬆ | ||
| IL-8 (CXCL8) | 15 | Ok | ✅ | 0.770 | 0.52–1.13 | 0.185 | ⬇ | ||
| IL-9 | 1 | Sparse Data | ❌ | 0.640 | 0.47–0.86 | 0.004 | ** | ⬇ | |
| IL-10 | 9 | Ok | ✅ | 1.029 | 0.65–1.62 | 0.901 | ⬆ | ||
| IL-15 | 7 | Ok | ✅ | 0.676 | 0.43–1.06 | 0.085 | . | ⬇ | |
| IL-17A/CTLA-8 | 2 | Sparse Data | ❌ | 1.236 | 0.85–1.79 | 0.264 | ⬆ | ||
| IL-18 | 15 | Ok | ✅ | 1.636 | 0.92–2.90 | 0.092 | . | ⬆ | |
| IL-31 | 1 | Sparse Data | ❌ | 1.155 | 0.63–2.11 | 0.639 | ⬆ | ||
| IP-10 (CXCL10) | 15 | Ok | ✅ | 1.166 | 0.83–1.64 | 0.377 | ⬆ | ||
| MCP-1 (CCL2) | 15 | Ok | ✅ | 0.494 | 0.31–0.80 | 0.004 | ** | ⬇ | |
| MIP-1α (CCL3) | 15 | Ok | ✅ | 0.811 | 0.44–1.50 | 0.502 | ⬇ | ||
| MIP-1β (CCL4) | 15 | Ok | ✅ | 0.849 | 0.57–1.25 | 0.412 | ⬇ | ||
| RANTES (CCL5) | 15 | Ok | ✅ | 0.988 | 0.65–1.49 | 0.953 | ⬇ | ||
| SDF-1α | 15 | Ok | ✅ | 0.979 | 0.60–1.60 | 0.933 | ⬇ | ||
| TNF-α | 3 | Sparse Data | ❌ | 0.555 | 0.32–0.97 | 0.038 | * | ⬇ | |
| 1 Number of samples with ≥1 measure(s) above the LOD across the 3 replicates. | |||||||||
| Associations between Reservoirs Measures and counts of migration events from the CNS to the periphery | ||||||||
|---|---|---|---|---|---|---|---|---|
| Negative Binomial Models (per transition) | ||||||||
| Reservoir Measures | Effect | Status | exp(Beta) | 95% CI | p-value | Significance | Direction | |
| HIV DNA (source) | Ok | ✅ | 0.875 | 7.0e-01–1.1e+00 | 0.224 | ⬇ | ||
| HIV DNA (destination) | Ok | ✅ | 1.007 | 8.5e-01–1.2e+00 | 0.932 | ⬆ | ||
| Viral Diversity (source) | Ok | ✅ | >1e6 | 1.7e+05–+Inf | 0.004 | ** | ⬆ | |
| Viral Diversity (destination) | Ok | ✅ | >1e6 | 9.4e-03–+Inf | 0.139 | ⬆ | ||
| Viral Divergence | Wide CI | ❌ | 5.247 | <1e-6–+Inf | 0.888 | ⬆ | ||
| Associations between Reservoirs Measures and counts of migration events from the periphery to the CNS | ||||||||
|---|---|---|---|---|---|---|---|---|
| Negative Binomial Models (per transition) | ||||||||
| Reservoir Measures | Effect | Status | exp(Beta) | 95% CI | p-value | Significance | Direction | |
| HIV DNA (source) | Ok | ✅ | 1.158 | 1.0e+00–1.3e+00 | 0.043 | * | ⬆ | |
| HIV DNA (destination) | Ok | ✅ | 0.959 | 8.4e-01–1.1e+00 | 0.525 | ⬇ | ||
| Viral Diversity (source) | Ok | ✅ | >1e6 | 5.6e+00–+Inf | 0.029 | * | ⬆ | |
| Viral Diversity (destination) | Wide CI | ❌ | 0.586 | <1e-6–+Inf | 0.951 | ⬇ | ||
| Viral Divergence | Wide CI | ❌ | 0.005 | <1e-6–+Inf | 0.605 | ⬇ | ||
| Associations between Reservoirs Measures and counts of migration events across the BBB | ||||||||
|---|---|---|---|---|---|---|---|---|
| Negative Binomial Models (per transition) | ||||||||
| Reservoir Measures | Effect | Status | exp(Beta) | 95% CI | p-value | Significance | Direction | |
| HIV DNA (source) | Ok | ✅ | 1.163 | 1.1e+00–1.3e+00 | 0.003 | ** | ⬆ | |
| HIV DNA (destination) | Ok | ✅ | 0.917 | 8.4e-01–1.0e+00 | 0.056 | . | ⬇ | |
| Viral Diversity (source) | Ok | ✅ | >1e6 | 1.0e+05–+Inf | 0.000 | *** | ⬆ | |
| Viral Diversity (destination) | Ok | ✅ | 0.193 | <1e-6–1.1e+05 | 0.808 | ⬇ | ||
| Viral Divergence | Ok | ✅ | 0.031 | <1e-6–9.3e+05 | 0.693 | ⬇ | ||
| Associations between Reservoirs Measures and counts of migration events within CNS | ||||||||
|---|---|---|---|---|---|---|---|---|
| Negative Binomial Models (per transition) | ||||||||
| Reservoir Measures | Effect | Status | exp(Beta) | 95% CI | p-value | Significance | Direction | |
| HIV DNA (source) | Ok | ✅ | 0.730 | 6.4e-01–8.4e-01 | 0.000 | *** | ⬇ | |
| HIV DNA (destination) | Ok | ✅ | 1.103 | 9.8e-01–1.2e+00 | 0.098 | . | ⬆ | |
| Viral Diversity (source) | Ok | ✅ | 2972.111 | 3.5e-05–+Inf | 0.391 | ⬆ | ||
| Viral Diversity (destination) | Ok | ✅ | 25988.049 | 5.1e-03–+Inf | 0.197 | ⬆ | ||
| Viral Divergence | Wide CI | ❌ | 57.962 | <1e-6–+Inf | 0.670 | ⬆ | ||
HIV Persistence & Dynamics | Research Presentation